Examining the Use of Non-Invasive Inhaled Nitric Oxide to Reduce Chronic Lung Disease in Premature Newborns

• Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality [ Time Frame: Week 36 or earlier, if participants are discharged from the hospital ]
  Number of participants that developed bronchopulmonary dysplasia and/or that died
  
  
• Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality Stratified by Birth Weight [ Time Frame: Randomization to discharge ]
  Number of participants that developed bronchopulmonary dysplasia and/or that died, stratified by birth weight (grams)
  
  

• Severity of Bronchopulmonary Dysplasia (BPD) [ Time Frame: 36 weeks corrected gestational age ]
  Assessment of the severity of BPD as defined by the oxygen reduction test
  
  
• Need for Mechanical Ventilation [ Time Frame: Anytime after randomization up to 36 weeks corrected gestational age ]
  Number of participants who required endotracheal intubation and mechanical ventilation
  
  
• Total Ventilation Days [ Time Frame: After randomization up until hospital discharge ]
  Of those participants who required mechanical ventilation, the total number of days receiving ventilation
  
  
• Necrotizing Enterocolitis (NEC) [ Time Frame: After randomization through hospital discharge ]
  Number of participants diagnosed with necrotizing enterocolitis
  
  
• Symptomatic PDA Requiring Medical Treatment [ Time Frame: From randomization until discharge ]
  Number of participants with a symptomatic PDA that required medical treatment
  
  
• Symptomatic PDA Requiring Surgical Ligation [ Time Frame: Randomization through discharge ]
  Number of participants with symptomatic PDA that required surgical ligation
  
  
• Threshold Retinopathy of Prematurity (ROP) [ Time Frame: Randomization to discharge ]
  Threshold ROP defined as requiring interventional therapy
  
  
• Severe Intracranial Hemorrhage [ Time Frame: Randomization to discharge ]
  Number of participants that developed severe intracranial hemorrhage (grade 3-4)
  
  
• Sepsis [ Time Frame: Randomization to discharge ]
  Number of participants that developed sepsis
  
  

• Days in Hospital [ Time Frame: From birth to hospital discharge ]
  Length of stay of participants
  
  

BPD is a serious lung condition that primarily affects premature newborns and newborns with low birth weights. iNO has been proven to be a safe and effective treatment for pulmonary hypertension and hypoxemic respiratory failure—both of which are abnormal lung conditions—in full-term newborns. However, in babies born prematurely, the effects of iNO on lung function are not well defined. Also, previous studies have mainly examined whether iNO reduces the incidence of BPD in newborns who are on mechanical ventilation. However, intubation and mechanical ventilation of premature newborns is now increasingly being avoided, and non-invasive support, including the use of nasal continuous positive airway pressure (NCPAP), is being used. Early treatment with low-dose iNO may reduce the incidence of BPD in premature newborns who do not require mechanical ventilation and intubation after delivery. The purpose of this study is to determine if low-dose, non-invasive iNO reduces the risk of BPD, pulmonary hypertension, and death in premature newborns who do not require mechanical ventilation.

This study will enroll premature newborns who require extra oxygen but do not require intubation or mechanical ventilation for respiratory failure in the first 72 hours of life. Participants will be randomly assigned to receive low-dose, non-invasive iNO or nitrogen (placebo) during their hospital stay. While hospitalized, participants' heart rate, blood oxygen level breathing rate, blood pressure, and medications will be monitored, and blood collection will occur at various times. Monitoring will continue until participants are 30 weeks corrected gestational age or for at least 14 days if participants are born at 29 weeks or more. All participants will undergo an ultrasound of the head when they are 7 days, 28 days, and 36 weeks of age. They will undergo an echocardiogram, which is an ultrasound of the heart, at 7 and 21 days of age and 4 weeks before the original expected due date. A chest x-ray will be performed before hospital discharge, and a breathing status test will be performed either 4 weeks before participants' original expected due date or before hospital discharge. Follow-up study visits will occur at Years 1 and 2, and will include a physical examination and developmental and behavioral testing. Another echocardiogram will also be performed at the Year 1 visit.